1. Director, Pediatric Allergy & Immunology
Acute Asthma: 2009 Update
Heather Lemon-Mulé, MD
Director, Pediatric Allergy & Immunology
St. Barnabas Hospital
July 28, 2009

2. Definition of Asthma
A chronic inflammatory disease of the lungs characterized by reversible airway obstruction and airway hyper-reactivity
Acute asthma exacerbations are paroxysmal episodes of wheeze, cough, tachypnea, dyspnea, hypoxia, respiratory failure

3. Etiology of Acute Exacerbations
Viral agents identified in >80% of pediatric asthma exacerbations and >50% of adult asthma exacerbations
Rhinovirus is identified in>65% of wheezing episodes caused by URIs
Peaks in hospital admissions for asthma correlate with RV seasons (spring and fall)
With use of RT-PCR as a supplement to viral culture viruses detected in >80% of pediatric asthma exacerbations.
When URI is suspected cause of asthma exacerbation, viral agent identified >90% of the time so clinical judgement is quite sensitiive

4. Acute Asthma Etiology
Pediatric Inf Disease Journal 2009: PICU admissions for 43 pts with LRTI; 30 specimens with identifiable infectious agent;

5. Etiology of Acute Asthma Exacerbations
Allergen exposure (aeroallergen)
Exercise
Atypical bacteria
GERD
Sinusitis
ASA/NSAID ingestion (AERD)

6. Pathophysiology
Asthma historically has been considered the prototypic atopic disease triggered by allergen exposure
Acute phase is triggered by allergen binding to IgE molecules bound to the FcEpsilon receptor on the mast cell surface in a sensitized individual
Allergen binding and cross-linking of t he IgE receptors sends a powerful stimulus for mast cell degranulation
Upon dgranulation is the release of pre-formed and newly synthesized mediators including histamine, proteases, leukotrienes as well as various pro-inflammatory cytokines and chemokines
Histamine and leukotrienes are both powerful agents of bronchoconstriction and histamine also promotes increased mucus production and viscosity leading to mucus plugging
Pro-inflamatory cytokines and chemokines initiate the chronic phase leading to recruitment of various cells, including eosinophils, lymphocytes, macrophages and to a lesser extent neutrophils
Wth prolonged and uncontrolled inflammation airway remodelling occurs; this is a result of fibroblast activation with collegen and other extracellular matric protein deposition as well as airway smooth muscle hyperplasia/hypertrophy and mucus gland hyperplasia
The end result of remodelling is loss of lung function essentially leading from a lung disease charactierized by reversible airway obstruction to one with irreversible airway obstruction.

7. Pathophysiology: Virus-Induced Wheezing
The pathophysiology of viral-induced wheezing is different.
Viral infections induce neutrophilic inflammation but also increased levels of eosinophils, CD4 and CD8 T-cells and mast cells through increased expression of pro-inflammatory cytokines and chemokines.
Viral infection also results in increased mucus secretion as well as respiratory epithelium shedding and release of mediators from neutrophils ans eosinophils that lead to bronchocontriction

8. Pathophysiology of Acute Asthma
Evidence of neutrophil degranulation and LDH levels are independent predictors of exacerbation severity.
RV infection leads to early release of IP-10 which is INF-γ-induced protein 10 (IP-10) and asthmatic pts have increased serum levels of IP-10 in response to Rv infection as compared with non-asthmatic controls; IP-10 levels correlate with airflow obstruction and high levels are associated with decreased bronchdilator response to B-agonists. RV infection also leads to increases expression of IL-6, IL-8, IL-16, eotaxin and RANTES which promote influx of other inflammatory cells as well, including eosinophils.
RV viral loads correlate with exacerbation severity.

9. Pathophysiology: Virus-Induced Wheezing
This slide shows the role of eosinophils in viral-induced asthma exacerbations.

10. RV in Asthma: Innate Immune Defect?
Interferons are anti-viral proteins produced in the innate immune response to viral infections
IFN-β induces apoptosis in infected cells; decreased production of IFN-β in asthmatics allows increased viral replication
Asthmatics also have decreased production of IFN-α and IFN-λ
RV has garnered a lot of interest over past decade b/c it really seems to pick out the asthmatics, specifically those who develop persistent atopic asthma.
There is increasing evidence that asthmatic patients (those with classica atopic asthma) are particularly susceptible to viral respiratory infections and RV especially because of an innate immune defect

11. Allergy and Viral Infections: Synergy?
Murray et al (Thorax 2006) showed allergen-exposed, atopic asthmatic children at greater risk for hospital admission with LRT viral infections
Similar findings in adult asthmatic patients (BMJ 2002)
Likely due to increased chronic airway inflammation in atopic asthmatic patients; asthmatics have increased expression of ICAM1 (this protein is upregulated in allergic inflammation and allows for leukocyte/lymphocyte adhesion to endothelium and transmigration into lung tissue); ICAM-1 is the binding receptor for RV and therefore at risk for more severe RV infections (greater infection rate and possibly innate immune defect)

12. Allergen Sensitization and Exposure
Exposure to seasonal allergens implicated in sudden asthma-related deaths
Alternaria sp exposure is associated with exacerbations and a 200-fold increased risk for respiratory arrest
HDM, cat and CR sensitization are RF for emergency treatment
Grass pollen sensitization (“thunderstorm asthma”) is associated with asthma exacerbation epidemics
No question that allergen exposure in an atopic asthmatic can trigger asthma exacerbations including life-threatening exacerbations

13. Role of Atypical Bacteria?
Cunningham et al (Eur Respir J 1998) showed strong correlation between C. pneumoniae-specific IgA in NLF and asthma exacerbation frequency in children
Wark et al (Eur Respir J 2002) found 38% of adults treated in ED for asthma exacerbations had serologic evidence of C. pneumoniae reactivation and greater lower airway inflammation
Both studies had high viral detection rates (85% and 76%)
These studies suggest that viral infections allow for C. pneumoniae reactivation possibly increasing the severity of the exacerbation

14. Role of Atypical Bacteria?
Johnston et al (NEJM 2006) performed RDBPCT with telithromycin in adult asthmatics experiencing acute exacerbations
>50% of patients had serologic evidence of infection but only 3 by PCR assay (C. pneumoniae)
Telithromycin treated patients had improved symptom scores, but not lung function compared with placebo
Unclear whether improvement due to antibacterial properties vs. immunomodulating properties
Improvement noted in patients with and without evidence of infection with atypical organisms
Improvement in telithromycin group statistically significant but of questionable clinical significance

15. Differential Diagnosis of Acute Asthma
Bronchiolitis (and other viral PNAs)
Croup
Bacterial Pneumonia (typical or atypical)
Foreign Body
Vocal Cord Dysfunction
Allergic Reaction
Panic Attack
Congestive Heart Failure
Pertussis
CF exacerbation

16. Determining Exacerbation Severity
Clinical signs and symptoms
Objective measurements (functional assessment)
Implications for management

17. Signs and Symptoms of Acute Asthma
Mild
Moderate
Severe
Impending Respiratory Arrest
Breathlessness
While walking
At rest (Infants – softer, shorter cry, difficulty feeding)
At rest (Infants – stops feeding)
Can lie down
Prefers sitting
Sits upright
Talks in
Sentences
Phrases
Words
Unable to speak
Alertness
May be agitated
Often agitated
Usually agitated
Drowsy or confused
Signs
Respiratory Rate
Often increased
Usually increased
Increased
May be decreased
Use of Accessory Muscles
Usually not
Commonly
Usually
Paradoxical thoracoabdominal movement
Wheeze
Often only end expiratory
Throughout expiration
Throughout inhalation/expiration
Absence of wheeze
Heart Rate
Usually normal
Often Bradycardic
Pulsus paradoxus
Absent (<10 mm Hg)
May be present (10-25 mm Hg)
Often Present (20-40 mm Hg) (>25 mm Hg adult)
Absence suggests respiratory muscle fatigue
Modified from NAEPP Guidelines 2007

18. Determining Severity: PEF
Symptoms & Signs
Initial PEF (or FEV1)
Clinical Course
Mild
Dyspnea only with activity (infants: tachypnea only and does not interfere with feeding)
PEF ≥70% predicted or personal best
Prompt relief with SABA;
Usually cared for at home;
Oral steroids usually not required
Moderate
Dyspnea interferes with or limits activity (may interfere with infant feeding)
PEF 40-69% predicted or personal best
Requires office/ED visit; Relief from frequent inhaled SABA; Oral steroids often required; sx last 1-2 days after Rx initiated
Severe
Dyspnea at rest; interferes with conversation (and infant feeding)
PEF <40% predicted or personal best
Usually requires ED visit and hospitalization; partial relief from SABA; oral steroids required; sx last >3 days after Rx initiated; adjunctive therapies helpful
Life Threatening
Too dyspneic to speak; perspiring
PEF < 25% predicted or personal best
Requires ED/hospitalization and probable ICU; poor response to SABA; IV steroids required; adjunctive therapies helpful

19. Determining Severity: Functional Assessment
Mild
Moderate
Severe
Subset: Life-Threatening
PEF (% predicted or personal best)
≥70
40-69 or response lasts < 2 ours
<40
<25 (may not be needed or pt may not be capable)
PaO2 (on RA)
and/or
PaCO2
Normal (test usually not required)
<42 mm Hg (test usually not required)
≥ 60 mm Hg (test usually not required)
<60 mm Hg: possible cyanosis
≥ 42 mm Hg: possible respiratory failure
SaO2 (on RA) at sea level
>95%
90-95%
<90%

20. RF for Asthma-Related Death: Asthma History
Previous severe exacerbations (especially history of ETI or ICU admission)
≥2 admissions for asthma within previous 12 months
≥3 ED visits for asthma within previous 12 months
Hospitalization or ED visit within past month
Use of >2 canisters of SABA/month
Difficulty perceiving asthma symptoms or severity of exacerbations

21. Other RF for Asthma-Related Death
Social: low SES or inner city residence, illicit drug use or other major psychosocial problems
Comorbidities: cardiovascular disease, other chronic lung disease, chronic psychiatric disease

22. Special Consideration: Infants
Infants high-risk group for respiratory failure
Greater peripheral airway resistance
Fewer collateral channels of ventilation
Further extension of airway smooth muscle into the peripheral airways
Less elastic recoil
Mechanical disadvantage of the diaphragm
Ventilation/perfusion characteristics promote hypoxemia more readily than older children/adults

23. Special Consideration: Infants
Use of accessory muscles, inspiratory/expiratory wheezing, paradoxical breathing, cyanosis and RR>60 suggest serious distress
SaO2<90% also sign of serious distress; SaO2<92% after 1 hour of treatment good indicator of need for hospitalization
Assessment largely determined by PE findings rather than objective measurements
Response to SABA can be variable; lack of response can be an indicator for admission

24. Initial Assessment: Brief History
Time of onset and any potential causes of current exacerbation
Severity of symptoms, especially compared with previous exacerbations, and response to any already given treatments
All current medications and time of last dose, especially of asthma medications
Any prior episodes of respiratory insufficiency due to asthma
Other potentially complicating illness
Estimate of number of previous unscheduled office visits, ED visits, and hospitalizations for asthma, particularly within the past year
(loss of consciousness or intubation and mechanical ventilation)
especially other pulmonary or cardiac disease or diseases that may be aggravated by systemic corticosteroid therapy (such as diabetes, peptic ulcer, hypertension, and psychosis).

25. Initial Assessment: Physical Examination
Assess the severity of the exacerbation: overall patient status, including level of alertness, fluid status, and presence of cyanosis, respiratory distress, and wheezing
Identify possible complications
Rule out upper airway obstruction
Clues to the presence of alternative reasons for dyspnea include dysphonia, inspiratory stridor, monophonic wheezing loudest over the central airway, normal values for PaO2, and unexpectedly complete resolution of airflow obstruction with intubation.
Wheezing can be an unreliable indicator of obstruction; in rare cases, extremely severe obstruction may be accompanied by a
“silent chest” (Shim and Williams 1980).
Complications: (ex. pneumonia, pneumothorax, pneumomediastinum); although rare, these will influence management of the asthma
exacerbation.
When upper airway obstruction is suspected, further evaluation is indicated by flow-volume curves and by referral for laryngoscopy
Both intrathoracic and extrathoracic central airway
obstruction can cause severe dyspnea and may be diagnosed as asthma. ♦ Causes include upper airway foreign bodies, epiglottitis, organic diseases of the larynx, vocal cord dysfunction, and extrinsic and intrinsic tracheal narrowing

26. Laboratory Studies: Indications
CXR: obtain if complicating process suspected
CBC: consider for patients with suspected serious bacterial infections
ABG: indicated in patients suspected of hypoventilation, severe distress or FEV1 or PEF ≤25% predicted or personal best after initial treatment
VBG: PCO2>45 mmHg may serve as a screening test but cannot substitute for an ABG
Serum electrolytes generally not indicated unless patient at risk for electrolyte disturbances
Most patients presenting with acute asthma do not require investigations
CXR: indicated if suspect CHF, PNA, pneumothorax, pneumonmediastinum, lobar atelectasis
CBC: asthma exacerbations can be associated with modest leukocytosis and corticosteroids cause neutrophil demargination with 1-2 hours of administration (mature PMNs not bands)
ABG: respiratory drive increased in patients with asthma exacerbations so normal PCO2 of 40 mm Hg indicates severe airflow obstruction and heightened risk of respiratory failure
Electrolytes: frequent SABA administration can lead to transient decreases in K, Mg and PO4; patients at risk for clinical symptoms include patients taking diuretics and those with pre-existing cardiac disease

27. Treatment Goals Correction of hypoxemia
Rapid reversal of airflow obstruction
Reduction of likelihood of relapse or recurrence of exacerbation

28. This is the algorithm for home management of asthma exacerbations.
Assess Severity
Patients at high risk for a fatal attack require immediate medical attention after initial treatment.
Symptoms and signs suggestive of a more serious exacerbation such as marked breathlessness, inability to speak more than short phrases, use of accessory muscles, or drowsiness should result in initial treatment while immediately consulting with a clinician.
Less severe signs and symptoms can be treated initially with assessment of response to therapy and further steps as listed below.
If available, measure PEF—values of 50–79% predicted or personal best indicate the need for
quick-relief mediation. Depending on the response to treatment, contact with a clinician may also be indicated. Values below 50% indicate the need for immediate medical care.
Initial Treatment
Inhaled SABA: up to two treatments 20 minutes apart of 2–6 puffs by MDI+ VHC or nebulizer treatments.
Good Response: No wheezing or dyspnea (assess tachypnea in young children). PEF ≥80% predicted or personal best.
Contact clinician for
follow-up instructions/management
May continue inhaled SABA every 3–4 hours for 24–48 hours.
Consider short course of oral systemic corticosteroids for high-risk patients
Incomplete Response: Persistent wheezing and dyspnea (tachypnea). PEF 50–79% predicted or personal best.
Add oral systemic corticosteroid.
Continue inhaled SABA.
Contact clinician urgently (this day) for further instruction.
Poor Response: Marked wheezing and dyspnea. PEF <50% predicted or personal best.
Repeat inhaled SABA immediately.
If distress is severe and nonresponsive to initial treatment:
—Call your doctor AND
—PROCEED TO ED;
—Consider calling 9–1–1
(ambulance transport).
To ED
This is the algorithm for home management of asthma exacerbations.
Modified from NAEPP Guidelines 2007

29. Modified from NAEPP Guidelines 2007
Initial Assessment
Brief history, physical examination , PEF or FEV1, oxygen saturation, and other tests as indicated.
Mild-to-Moderate (FEV1 or PEF ≥40%)
Oxygen to achieve SaO2 ≥90%
SABA up to 3 doses in first hour
Oral CS if no immediate response or recently took oral CS or high-risk patient
Severe (FEV1 or PEF <40%)
SABA + ipratropium q20min or continuously for 1h; Oral CS
Impending or Actual Respiratory Arrest
Intubation and mechanical ventilation (FiO2 1.0)
Nebulized SABA + ipratropium; consider adjunct therapies; Intravenous CS
Repeat Assessment
Symptoms, physical examination, PEF, O2 saturation, other tests as needed
Moderate Exacerbation
Physical exam: moderate symptoms; FEV1 or PEF 40–69%
Inhaled SABA q1h; Oral CS
Continue treatment 1–3 hours if improvement; make admit decision in <4 hours
Severe Exacerbation
Physical exam: severe symptoms at rest, accessory muscle use, chest retractions; FEV1 or PEF <40%. History: high-risk patient.
No improvement after initial treatment: Oxygen, Nebulized SABA + ipratropium, hourly or continuous; consider adjunct therapies, Oral CS
Good Response (FEV1 or PEF ≥70%)
Response sustained 1 hr after last SABA Physical exam: normal; no distress
Incomplete Response (FEV1 or PEF 40–69%)
Mild-to-moderate symptoms
Poor Response (FEV1 or PEF <40%)
PCO2 ≥42 mm Hg
Physical exam: symptoms severe,
drowsiness, confusion
Individualized decision re: hospitalization
Discharge Home
Continue inhaled SABA.
Continue course of oral CS.
Consider initiation of an ICS.
Patient education:
− Review medications, including inhaler technique.
− Review/initiate action plan.
− Recommend close medical follow-up
Admit to Hospital Ward
Oxygen
Inhaled SABA
Systemic (oral or intravenous) CS
Consider adjunct therapies
Monitor vital signs, FEV1 or PEF, SaO2
Admit to Hospital Intensive Care
Inhaled SABA hourly or continuously
Intravenous CS
Possible intubation and mechanical ventilation
Improve
Continue treatment with inhaled SABAs.
Continue course of oral CS
Continue on or consider initiating ICS.
Patient education (e.g., review meds, including inhaler technique, environmental control measures; review/initiate action plan; recommend close medical follow-up.
Schedule follow-up appointment with PMD and/or asthma specialist in 1–4 weeks.
This is the treatment algorithm for management of exacerbations in the ED.
PE as well as FEV1/PEF measurements if capable determines severity: auscultation, use of accessory muscles, heart rate, respiratory rate
Modified from NAEPP Guidelines 2007

30. Inhaled SABA Onset of action within 5 minutes
Peak effect in minutes
Duration of action 4-6 hours
Promote bronchodilation by smooth muscle relaxation
May be given intermittently or continuously (nebulized)
First line therapy for the relief of asthma symptoms are the inhaled SAB2A
B2-specific

31. Inhaled SABAs
Medication
Children ≤ 12 years old
Children > 12 years old
Comments
Albuterol nebulizer solution (0.63 mg/3 ml, 1.25 mg/3 ml, 2.5 mg/3 ml, 5 mg/ml)
0.15 mg/kg (min of 2.5 mg) q20mins for 3 doses then mg/kg (max 10 mg)
q1-4h prn OR 0.5 mg/kg/hr continuous nebulization
2.5-5 mg q20mins for 3 doses then mg q1-4h prn OR mg/hr continuously
Dilute aerosols to minimum of 3 ml; gas flow at 6-8 L/min.
Albuterol MDI (90 mcg/puff)
4-8 puffs q20min for 3 doses then q1-4h prn; use VHC; add mask in children <4 years old
4-8 puffs q20min up to 4 doses then q1-4h prn
MDI plus VHC equally efficacious as nebulized therapy in mild-moderate exacerbations
Levalbuterol nebulizer solution (0.63 mg/3 ml, 1.25 mg/0.5 mL, 1.25 mg/3 mL)
0.075 mg/kg (min dose 1.25 mg) q20min for 3 doses then mg/kg up to 5 mg q1-4h prn
mg q20min for 3 doses then mg q1-4h prn
Comparable efficacy to albuterol; not evaluated by continuous nebulization
Levalbuterol MDI (45 mcg/puff)
Same as albuterol MDI dosing
Albuterol also comes in an oral preparation but this is generally not indicated, especially in the acute asthma setting due to it’s delay in onset and increased systemic side-effects.

32. Modified from NAEPP Guidelines 2007
Initial Assessment
Brief history, physical examination , PEF or FEV1, oxygen saturation, and other tests as indicated.
Mild-to-Moderate (FEV1 or PEF ≥40%)
Oxygen to achieve SaO2 ≥90%
SABA up to 3 doses in first hour
Oral CS if no immediate response or recently took oral CS or high-risk patient
Severe (FEV1 or PEF <40%)
SABA + ipratropium q20min or continuously for 1h; Oral CS
Impending or Actual Respiratory Arrest
Intubation and mechanical ventilation (FiO2 1.0)
Nebulized SABA + ipratropium; consider adjunct therapies; Intravenous CS
Repeat Assessment
Symptoms, physical examination, PEF, O2 saturation, other tests as needed
Moderate Exacerbation
Physical exam: moderate symptoms; FEV1 or PEF 40–69%
Inhaled SABA q1h; Oral CS
Continue treatment 1–3 hours if improvement; make admit decision in <4 hours
Severe Exacerbation
Physical exam: severe symptoms at rest, accessory muscle use, chest retractions; FEV1 or PEF <40%. History: high-risk patient.
No improvement after initial treatment: Oxygen, Nebulized SABA + ipratropium, hourly or continuous; consider adjunct therapies, Oral CS
Good Response (FEV1 or PEF ≥70%)
Response sustained 1 hr after last SABA Physical exam: normal; no distress
Incomplete Response (FEV1 or PEF 40–69%)
Mild-to-moderate symptoms
Poor Response (FEV1 or PEF <40%)
PCO2 ≥42 mm Hg
Physical exam: symptoms severe,
drowsiness, confusion
Individualized decision re: hospitalization
Discharge Home
Continue inhaled SABA.
Continue course of oral CS.
Consider initiation of an ICS.
Patient education:
− Review medications, including inhaler technique.
− Review/initiate action plan.
− Recommend close medical follow-up
Admit to Hospital Ward
Oxygen
Inhaled SABA
Systemic (oral or intravenous) CS
Consider adjunct therapies
Monitor vital signs, FEV1 or PEF, SaO2
Admit to Hospital Intensive Care
Inhaled SABA hourly or continuously
Intravenous CS
Possible intubation and mechanical ventilation
Improve
Continue treatment with inhaled SABAs.
Continue course of oral CS
Continue on or consider initiating ICS.
Patient education (e.g., review meds, including inhaler technique, environmental control measures; review/initiate action plan; recommend close medical follow-up.
Schedule follow-up appointment with PMD and/or asthma specialist in 1–4 weeks.
For the treatment of severe exacerbations the NAEPP guidelines recommend the addition of inhaled ipratropium to SABA treatments
Modified from NAEPP Guidelines 2007

33. Inhaled Anticholinergics
Medication
Children ≤12 yo
Children >12 yo
Comments
Ipratropium bromide
Nebulized solution
(0.25 mg/ml)
mg q20min for 3 doses, then prn
0.5 mg q20min for 3 doses then prn
Added to SABA during severe exacerbations; no proven benefit for mild/moderate exacerbations; no proven benefit once patient hospitalized
MDI (18 mcg/puff)
4-8 puffs q20min prn up to 3 hours
8 puffs q20min prn up to 3 hours
Children should use VHC; studies have examined MDI up to 3 hours only
Ipratropium bromide with albuterol
Nebulized solution (each vial contains 0.5 mg ipratropium and 2.5 mg albuterol)
1.5-3 ml q20min for 3 doses then prn
3 ml q20min for up to 3 doses then prn
Reserved for first 3 hours of treatment of severe exacerbations; no proven benefit once patient hospitalized
Ipratropium bromide with albuterol MDI (18 mcg ipratropium and 90 mcg albuterol per puff)
Children should use VHC; indications as above

34. Systemic Corticosteroids
Prednisone/Methylprednisolone/Prednisolone
Children ≤ 12 yo: 1-2 mg/kg/day (max 60 mg/day) for 3-10 days until PEF is 70% predicted or personal best
Children >12 yo: mg/day for 3-10 days until PEF is 70% predicted or personal best
Outpatient burst 1-2 mg/kg/day for 3-10 days
Tapers not required for courses less than 1 week; 10 day courses do no need to be tapered if patients taking ICS chronically

35. Preschool Wheezers: The Great CS Debate
Panickar et al (NEJM 2009) performed RDBPCT comparing oral prednisolone to placebo in 687 children between ages of 10 and 60 months
Majority of children experienced mild-moderate wheezing
Primary outcome was length of hospitalization; secondary outcomes were PRAM score, albuterol use and 7-day symptom scores
PRAM pre=school respiratory assessmetnt measure

36. Preschool Wheezers: The Great CS Debate
Prednisolone no better than placebo for any outcome
Study strengths: RDBPCT, large number of patients, use of standardized scoring (PRAM), majority of patients with viral wheezer phenotype
Limitations: possibly under-dosing of prednisolone for a significant number of patients, lack of data on subjects refusing participation, no provision of age of patients at high-risk for persistent asthma, no viral studies
Prednisone was also no better than placebo in subjects at high risk for the devlopemnt of persistent wheezing (atopic asthma)
Underdosing: 10 mg for children <2, 20 mg for older children would often work out to <1 mg/kg/day
PRAM- preschool respiratory assessment measure; validated against lung function measurements

37. Preschool Wheezers: The Great CS Debate
Several other studies have found contradictory results, particularly in patients at high-risk for the development of atopic asthma (positive API)
Recent study found reduced rate of relapse in subjects infected with RV when treated with prednisolone as compared to placebo
Study by Ducharme et al (NEJM 2009) showed decreased exacerbation severity in subjects treated with high-dose inhaled fluticasone at the onset of a URI-induced exacerbation
API:>4 wheezing episodes, parental h/o asthma, personal h/o physician-diagnosed AD
Minor: sensitization to food or aeroallergen, eosinophilia, wheezing without a cold
Ducharme study: used use of rescue oral CS as primary endpoint (surrogate for exacerbation severity)
Other studies have also shown intermittent use of inhaled CS and LTRA reduce symptoms during a URI-induced exacerbation

38. Systemic Corticosteroids: Summary
Always indicated for patients with severe exacerbations
Generally not indicated for patients with mild exacerbations unless high-risk for asthma-related death
Indicated for patients with moderate exacerbations if no immediate response to SABA treatment or high-risk for asthma-related death

39. Modified from NAEPP Guidelines 2007
Initial Assessment
Brief history, physical examination , PEF or FEV1, oxygen saturation, and other tests as indicated.
Mild-to-Moderate (FEV1 or PEF ≥40%)
Oxygen to achieve SaO2 ≥90%
SABA up to 3 doses in first hour
Oral CS if no immediate response or recently took oral CS or high-risk patient
Severe (FEV1 or PEF <40%)
SABA + ipratropium q20min or continuously for 1h; Oral CS
Impending or Actual Respiratory Arrest
Intubation and mechanical ventilation (FiO2 1.0)
Nebulized SABA + ipratropium; consider adjunct therapies; Intravenous CS
Repeat Assessment
Symptoms, physical examination, PEF, O2 saturation, other tests as needed
Moderate Exacerbation
Physical exam: moderate symptoms; FEV1 or PEF 40–69%
Inhaled SABA q1h; Oral CS
Continue treatment 1–3 hours if improvement; make admit decision in <4 hours
Severe Exacerbation
Physical exam: severe symptoms at rest, accessory muscle use, chest retractions; FEV1 or PEF <40%. History: high-risk patient.
No improvement after initial treatment: Oxygen, Nebulized SABA + ipratropium, hourly or continuous; consider adjunct therapies, Oral CS
Good Response (FEV1 or PEF ≥70%)
Response sustained 1 hr after last SABA Physical exam: normal; no distress
Incomplete Response (FEV1 or PEF 40–69%)
Mild-to-moderate symptoms
Poor Response (FEV1 or PEF <40%)
PCO2 ≥42 mm Hg
Physical exam: symptoms severe,
drowsiness, confusion
Individualized decision re: hospitalization
Discharge Home
Continue inhaled SABA.
Continue course of oral CS.
Consider initiation of an ICS.
Patient education:
− Review medications, including inhaler technique.
− Review/initiate action plan.
− Recommend close medical follow-up
Admit to Hospital Ward
Oxygen
Inhaled SABA
Systemic (oral or intravenous) CS
Consider adjunct therapies
Monitor vital signs, FEV1 or PEF, SaO2
Admit to Hospital Intensive Care
Inhaled SABA hourly or continuously
Intravenous CS
Possible intubation and mechanical ventilation
Improve
Continue treatment with inhaled SABAs.
Continue course of oral CS
Continue on or consider initiating ICS.
Patient education (e.g., review meds, including inhaler technique, environmental control measures; review/initiate action plan; recommend close medical follow-up.
Schedule follow-up appointment with PMD and/or asthma specialist in 1–4 weeks.
This is the treatment algorithm for management of exacerbations in the ED.
PE as well as FEV1/PEF measurements if capable determines severity: auscultation, use of accessory muscles, heart rate, respiratory rate
Modified from NAEPP Guidelines 2007

40. Magnesium Sulfate (IV)
Meta-analyses (adult and peds studies) show that hospitalization rates decreased when MgSO4 added to conventional Rx for severe exacerbations
Dose mg/kg up to 2 g
NAEPP recommendation: “consider in patients with life-threatening exacerbations and patients who remain in the severe category after 1 hour of intensive conventional therapy”
Severe exacerbations: PF<40%; no apparent value for pts with mild/moderate exacerbations
Not all studies have shown positive effect
Nebulized MgSO4 has shown some improvement in lung function in several trials but not adequate evidence to date

41. Heliox
Theoretical benefit for improving gas exchange because of helium’s low density
Studies contradictory
Three studies (1 peds, 2 adult) showed improvement in subjects experiencing moderate-severe exacerbations treated with Heliox-driven SABA treatments when compared to subjects receiving O2-driven SABA treatments
Discrepancies may be due to small sample sizes as well as failure to account for the different effect of heliox vs. oxygen on respirable mass (did not increase gas flow rate with heliox treatments).

42. Leukotriene Receptor Antagonists
RT showed significant improvement in pulmonary function within 10 minutes of administration of IV montelukast to patients with moderate-severe exacerbations
Oral montelukast does not take effect before 90 minutes from time of administration

43. Systemic β2 Agonists Medication Children<12 yo Children ≥12 yo
Comments
Epinephrine
1:1000 (1 mg/ml)
0.01 mg/kg up to mg sq q20min for 3 doses
mg sq q20min for up to 3 doses
No proven benefit over aerosol
Terbutaline (1 mg/ml)
0.01 mg/kg sq q20min for up to 3 doses then q2-6h prn
0.25 mg sq q20min for up to 3 doses

44. When to Intubate Signs of impending respiratory failure:
Inability to speak
Altered mental status
Worsening fatigue
Significant and prolonged retractions
PCO2 ≥ 42 mm Hg
Theoretical benefit of ketamine as a premedication for ETI has not born out in studies (limited data)

45. Assessing Response to Treatment
Serial physical examinations
Serial FEV1 or PEF
Serial pulse oximetry measurements
Signs and symptom scores
FEV1/PEF maneuvers almost impossible for children <5 yo
Study by Gorelick et al found that only 65% of children 5-18 yo could perform these tests adequately during exacerbation

46. Predicting Need for Hospitalization
Kelly et al (Respir Med 2004) showed that severity assessment at 1hour after initial treatment with SABA was better predictor of need for hospitalization than initial assessment
After 1hour if meets criteria for severe exacerbation >86% chance of hospitalization; if moderate after 1 hour >84% chance of hospitalization; if mild then only 18% chance of hospitalization
SaO2 <92-94% at 1 hour better predictor of need to hospitalize than initial SaO2

47. Modified from NAEPP Guidelines 2007
Initial Assessment
Brief history, physical examination , PEF or FEV1, oxygen saturation, and other tests as indicated.
Mild-to-Moderate (FEV1 or PEF ≥40%)
Oxygen to achieve SaO2 ≥90%
SABA up to 3 doses in first hour
Oral CS if no immediate response or recently took oral CS or high-risk patient
Severe (FEV1 or PEF <40%)
SABA + ipratropium q20min or continuously for 1h; Oral CS
Impending or Actual Respiratory Arrest
Intubation and mechanical ventilation (FiO2 1.0)
Nebulized SABA + ipratropium; consider adjunct therapies; Intravenous CS
Repeat Assessment
Symptoms, physical examination, PEF, O2 saturation, other tests as needed
Moderate Exacerbation
Physical exam: moderate symptoms; FEV1 or PEF 40–69%
Inhaled SABA q1h; Oral CS
Continue treatment 1–3 hours if improvement; make admit decision in <4 hours
Severe Exacerbation
Physical exam: severe symptoms at rest, accessory muscle use, chest retractions; FEV1 or PEF <40%. History: high-risk patient.
No improvement after initial treatment: Oxygen, Nebulized SABA + ipratropium, hourly or continuous; consider adjunct therapies, Oral CS
Good Response (FEV1 or PEF ≥70%)
Response sustained 1 hr after last SABA Physical exam: normal; no distress
Incomplete Response (FEV1 or PEF 40–69%)
Mild-to-moderate symptoms
Poor Response (FEV1 or PEF <40%)
PCO2 ≥42 mm Hg
Physical exam: symptoms severe,
drowsiness, confusion
Individualized decision re: hospitalization
Discharge Home
Continue inhaled SABA.
Continue course of oral CS.
Consider initiation of an ICS.
Patient education:
− Review medications, including inhaler technique.
− Review/initiate action plan.
− Recommend close medical follow-up
Admit to Hospital Ward
Oxygen
Inhaled SABA
Systemic (oral or intravenous) CS
Consider adjunct therapies
Monitor vital signs, FEV1 or PEF, SaO2
Admit to Hospital Intensive Care
Inhaled SABA hourly or continuously
Intravenous CS
Possible intubation and mechanical ventilation
Improve
Continue treatment with inhaled SABAs.
Continue course of oral CS
Continue on or consider initiating ICS.
Patient education (e.g., review meds, including inhaler technique, environmental control measures; review/initiate action plan; recommend close medical follow-up.
Schedule follow-up appointment with PMD and/or asthma specialist in 1–4 weeks.
Once the patient is hospitalized treatment is continued with O2, SABA q1-4h as needed or continuously if severe and systemic CS. Adjunct therapies may be continues as well but there is no proven benefit of continuing ipratropium treatments once patiets are admitted.
Modified from NAEPP Guidelines 2007

48. Plan for Discharge
Provide patients written instructions regarding dose, frequency and correct use of medications
Consider initiating or continue with ICS
Schedule follow-up appointment with PMD or asthma specialist within 4 weeks
Moderate exacerbations can have some sx for 1-2 days after initial treatment; severe exacerbations may be prolonged >3 days